Publications by authors named "Pascal Demoly"

285 Publications

Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.

Clin Exp Allergy 2021 Sep 18. Epub 2021 Sep 18.

Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant.

Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study.

Methods: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made.

Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without.

Conclusions & Clinical Relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.
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http://dx.doi.org/10.1111/cea.14019DOI Listing
September 2021

Drug Allergy Management on the Move.

J Allergy Clin Immunol Pract 2021 08;9(8):3021-3022

Rochester Regional Health, Rochester, NY; University of Rochester, Rochester, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.04.009DOI Listing
August 2021

Anaphylaxis and Pregnancy: A Systematic Review and Call for Public Health Actions.

J Allergy Clin Immunol Pract 2021 Aug 5. Epub 2021 Aug 5.

Allergy Department, University Hospital of Montpellier, Montpellier, France; Desbrest Institute of Epidemiology and Public Health, University of Montpellier, France; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn, USA; World Health Organization Collaborating Centre on Scientific Classification Support, Montpellier, France; Hospital Sírio-Libanês, São Paulo, Brazil. Electronic address:

Background: Although rare, anaphylaxis during pregnancy implies a risk to both mothers and newborns.

Objective: This systematic review is intended to identify key issues in the diagnosis and management of this condition to support prevention strategies and decrease the risk for death related to anaphylaxis during pregnancy.

Methods: We searched MEDLINE, Cochrane, LILACS, SciELO, and Science Direct databases for manuscripts concerning the term "anaphylaxis during pregnancy," without language restrictions. We screened studies, extracted data, and assessed the risk for bias independently in duplicate.

Results: We selected 12 articles. Frequency of anaphylaxis during maternity was estimated to be 1.5 to 3.8 per 100,000 pregnancies. Only one study provided anaphylaxis mortality data in pregnant women; the rate of anaphylaxis-related maternal mortality was estimated at 0.05/100,000 live births. No standard definition of anaphylaxis severity has been used. A total of 49% to 74% of anaphylaxis cases were described during caesarean section. Beta-lactam antibiotics (58%), latex (25%), and anesthetic agents (17%) were the main causes. In 17% of reports, causative agents were proven by allergy testing. Moreover, 72% of articles proposed the same management and treatment for a clinical episode of anaphylaxis during pregnancy as for nonpregnant patients, and the use of epinephrine in the patient's care during anaphylaxis in pregnancy.

Conclusions: Few studies address anaphylaxis during pregnancy. Most have been produced by nonallergy specialists. Collaboration among different specialists involved in the care of pregnant women should be established to support preventive strategies and reduce avoidable deaths.
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http://dx.doi.org/10.1016/j.jaip.2021.07.046DOI Listing
August 2021

Anaphylaxis and Coronavirus Disease 2019 vaccine: a danger relationship?

Curr Opin Allergy Clin Immunol 2021 10;21(5):411-417

Institut Desbrest d'Epidémiologie et de Santé Publique, IDESP UMR UA11 INSERM, University of Montpellier.

Purpose Of Review: Anaphylactic reactions reported after Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) RNA vaccines were expected to be more frequent in atopic subjects and attributed to its polyethylene glycol component.

Recent Findings: Anaphylaxis to SARS-CoV2 RNA vaccines is no more frequent than in any vaccine and direct proofs for the role of its polyethylene glycol component are lacking.

Summary: Vaccines against coronavirus disease 2019 (COVID-19) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have rapidly been reported after SARS-CoV2 RNA vaccines. This risk is now measured at 2.5-11/1 000 000 in the context of vaccine safety surveillance programs and only one case was documented to be due to polyethylene glycol. Suggestions for its role are indirect. The COVID-19 vaccination is rolling out vastly and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care, highlighting the key role of allergists in the vaccination programmes.
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http://dx.doi.org/10.1097/ACI.0000000000000778DOI Listing
October 2021

Worsening of chronic house-dust-mite-induced respiratory allergies: An observational survey in three European countries.

World Allergy Organ J 2021 Jul 7;14(7):100563. Epub 2021 Jul 7.

Allergy Service, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.

Background: Although respiratory allergies to house dust mites (HDMs) can often be controlled with symptomatic medications, some patients do not achieve satisfactory disease control.

Objective: To assess fortnightly fluctuations (notably worsening and/or exacerbations) in disease parameters among patients taking only symptomatic medications for HDM allergy.

Methods: In a 13-month, observational, multicenter survey of adults with a self-reported history of poorly controlled, moderate-to-severe, physician-diagnosed HDM respiratory allergy in France, Italy, and Spain, fortnightly telephone interviews were used to gather information on medication use, symptoms, the disease burden, and medical consultations from late May 2012 to early July 2013.

Results: A total of 313 patients completed the study ( = 114 in Italy, 92 in France, and 107 in Spain). Although most participants reported improvements in symptoms, a substantial minority (ranging from 12% to 44% per fortnightly telephone interview in 2012 and from 16% to 37% in 2013) complained of worsening. A few study participants did not improve at any time in the study: 4% overall, and 2%, 2%, and 7% in Italy, France and Spain, respectively. A change in the weather and/or contact with other allergens were the most frequent self-reported reasons for worsening, although the answer "I don't know" was also prominent.

Conclusion: In a 13-month survey of patients with HDM allergy in Italy, France, and Spain, the participants' symptom status fluctuated significantly - illustrating the complexity of this condition. Although most participants reported improvements, the "never-improver" profile warrants further investigation. More prominence could be given to symptom control and a low exacerbation risk as treatment goals in allergic rhinitis.
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http://dx.doi.org/10.1016/j.waojou.2021.100563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271175PMC
July 2021

Food-induced anaphylaxis morbidity: Emergency department and hospitalization data support preventive strategies.

Pediatr Allergy Immunol 2021 Jun 17. Epub 2021 Jun 17.

University Hospital of Montpellier, Montpellier, France.

Background: Anaphylaxis is a recognized public health issue. There is no doubt that food-induced anaphylaxis (FIA) has tremendous impact on the quality of life of patients and their families and increases direct and indirect costs. FIA is associated with increasing rates of emergency department admissions and hospitalizations and implies the risk of death. Morbidity epidemiological data are a key to tailor public health actions to this non-communicable disease. The aim of this article was to review published morbidity epidemiological data relating to FIA and potential risk factors, in order to provide evidence-based recommendations to reduce the risk of severe adverse outcomes.

Methods: We identified published studies available in PUBMED/MEDLINE (1966-2020), EMBASE (1980-2020) and CINAHL (1982-2020). The systematic review was carried out using MeSH terms related to FIA ED admissions and hospitalizations.

Results: A total of 25 articles were selected, 80% published in the last 5 years. After critical analysis of methodological and clinical characteristics reported in the data selected, we were able to propose preventive strategies.

Conclusion: Anaphylaxis is a recognized public health issue. FIA is associated with increasing rates of ED admissions and hospitalizations and imply in risk of death. More than reviewing and critically interpreting the key patterns related to FIA morbidity published data, we proposed strategies in order to promote quality care of patients suffering from FIA. Our World Health Organization Collaborative Center is deeply involved in this process, and we believe that the proposed strategies will inform future healthcare policies on anaphylaxis. The long-term objective would be to improve clinical care and quality of life of patients and their families, and develop risk-stratified, cost-effective preventive measures.
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http://dx.doi.org/10.1111/pai.13578DOI Listing
June 2021

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.

World Allergy Organ J 2021 May 18;14(5):100544. Epub 2021 May 18.

Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations.

Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex.

Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey.

Results: Among asthmatic subjects, higher percentage declines of FEV and FEV/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV and FeNO levels in non-smokers and women, regardless of asthma status.

Conclusions: We found a relationship between elevated FeNO and larger FEV decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.
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http://dx.doi.org/10.1016/j.waojou.2021.100544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142084PMC
May 2021

SARS-CoV-2 Vaccination and Anaphylaxis: Recommendations of the French Allergy Community and the Montpellier World Health Organization Collaborating Center.

Vaccines (Basel) 2021 May 27;9(6). Epub 2021 May 27.

Division of Allergy, Département de Pneumologie et Addictologie, University Hospital of Montpellier, 34295 Montpellier, France.

Vaccines against COVID-19 (and its emerging variants) are an essential global intervention to control the current pandemic situation. Anaphylactic reactions have been reported after SARS-CoV2 RNA vaccines. Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. This risk is estimated at 1/1,000,000 in the context of vaccine safety surveillance programs. The COVID-19 vaccination is rolling-out vastly in different courtiers and surveillance programs are key to monitor severe adverse reactions, such as anaphylaxis. Anaphylaxis due to vaccine is extremely rare and specific cases should receive individualized investigation and care. The here presented recommendations and follow-up from the French allergy community and the Montpellier WHO Collaborating Center in order to support the vaccination program and intends to support to healthcare professionals in their daily basis.
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http://dx.doi.org/10.3390/vaccines9060560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228790PMC
May 2021

Blood pressure measurements could be reduced in number during the drug provocation test.

Clin Exp Allergy 2021 Sep 12;51(9):1233-1237. Epub 2021 May 12.

Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France.

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http://dx.doi.org/10.1111/cea.13890DOI Listing
September 2021

Biologicals for the prevention of anaphylaxis.

Curr Opin Allergy Clin Immunol 2021 06;21(3):303-308

University Hospital of Montpellier.

Purpose Of Review: To review the use of biological agents (BA) in the treatment of anaphylaxis in the view of the new knowledge in the field to support the quality of care and prevention.

Recent Findings: Some BA, as a single medication or as combined therapy to food or venom immunotherapy, are effectively able to reduce most of the severe anaphylactic reactions.

Summary: Anaphylaxis is a recognized clinical emergency, which requires prompt identification and treatment. Several biologic therapies and new devices are emerging as a potential preventive treatment for anaphylaxis. However, adrenaline (epinephrine) is still the first-line treatment for any type of anaphylaxis. Biological drugs, such as omalizumab, whereas not US Food and Drug Administration (FDA) nor European Medicines Agency (EMA) approved for anaphylaxis, have been used as therapeutic adjuvants in the preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually.
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http://dx.doi.org/10.1097/ACI.0000000000000737DOI Listing
June 2021

Hypersensitivity reactions to platinum-based compounds in the context of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Description and management.

Allergy 2021 06 22;76(6):1882-1885. Epub 2020 Dec 22.

Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Univ Montpellier, Montpellier, France.

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http://dx.doi.org/10.1111/all.14679DOI Listing
June 2021

Epidemiology of anaphylaxis.

Curr Opin Allergy Clin Immunol 2021 04;21(2):168-174

University Hospital of Montpellier, Montpellier, and Desbret Institute of Epidemiology and Public Health, University of Montpellier, Montpellier, France.

Purpose Of Review: To understand the current global epidemiological data of anaphylaxis and identify potential strategies to improve patients' care and prevention.

Recent Findings: Anaphylaxis mortality and morbidity statistics (MMS) may gain new perspectives with the implementation of the International Classification of Diseases (ICD)-11 in the forthcoming years. Improving the quality of epidemiological data related to anaphylaxis should clarify some areas of uncertainty about risk factors, leading to better targeting of strategies to protect those patients at risk, and support decision-making to facilitate healthcare planning and implementation of public health measures to prevent anaphylaxis.

Summary: Anaphylaxis is a complex noncommunicable diseases with adverse impact on health-related quality of life of patients and their carriers and a significant proportion of deaths may be preventable. It requires an integrated holistic plan to improve quality of healthcare and gathering accurate and comparable epidemiological data is key. Morbidity related to anaphylaxis seems to be increasing worldwide whereas mortality of anaphylaxis appears to be low and stable, but this still has great challenges in capturing quality anaphylaxis MMS. Improving the quality of epidemiological data related to anaphylaxis should clarify some areas of uncertainty about risk factors, leading to better targeting of strategies to protect those patients at risk. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to anaphylaxis in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and better facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions.
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http://dx.doi.org/10.1097/ACI.0000000000000722DOI Listing
April 2021

Allergy and coronavirus disease (COVID-19) international survey: Real-life data from the allergy community during the pandemic.

World Allergy Organ J 2021 Feb 31;14(2):100515. Epub 2021 Jan 31.

Department of Medicine, Allergy Asthma and Clinical Immunology Section, University Hospital of Verona, Verona Italy.

Background: The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic.

Methods: We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-based questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context.

Results: Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as "I have no data" or "I don't know" to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations.

Conclusion: The data presented are a starting point in the process of getting feedback on all the recommendations provided by the allergy societies; it could also be the basis of new strategies to support health professionals while new COVID-19 specific treatments and vaccines are being explored. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and it should be helpful to health systems.
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http://dx.doi.org/10.1016/j.waojou.2021.100515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847410PMC
February 2021

The six million dollar man.

ERJ Open Res 2021 Jan 18;7(1). Epub 2021 Jan 18.

Dept of Respiratory Diseases, University of Montpellier, Montpellier, France.

https://bit.ly/2GykNtI.
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http://dx.doi.org/10.1183/23120541.00341-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836671PMC
January 2021

Revisiting Late-Onset Asthma: Clinical Characteristics and Association with Allergy.

J Asthma Allergy 2020 31;13:743-752. Epub 2020 Dec 31.

Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA.

The Global Initiative for Asthma (GINA) 2020 defines late-onset asthma (LOA) as one of the clinical phenotypes of asthma wherein patients, particularly women, present with asthma for the first time in adult life, tend to be non-allergic and often require higher doses of inhaled corticosteroids (ICS) or are relatively refractory to corticosteroid treatment. In this review, we examine the published literature improve the understanding of the following aspects of LOA: 1) the age cut-off for its diagnosis; 2) its distinct clinical phenotypes, characteristics and risk factors; and 3) its association with allergic comorbidities and conditions. Overall, our review reveals that clinicians and researchers have used multiple age cut-offs to define LOA, with cut-off ages ranging from >12 years to ≥65 years. LOA has also been classified into several distinct phenotypes, some of which drastically differ in their clinical characteristics, course and prognosis. Although LOA has traditionally been considered non-allergic in nature, our review indicates that it is commonly associated with allergic features and comorbidities. Our findings suggest that there is an urgent need for the development of more clear clinical practice guidelines that can provide more clarity on the definition and other aspects of LOA. In addition, the association of LOA and allergy needs to be re-examined to frame a more optimal treatment strategy for patients with LOA.
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http://dx.doi.org/10.2147/JAA.S282205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781019PMC
December 2020

Cephalosporin Hypersensitivity: Descriptive Analysis, Cross-Reactivity, and Risk Factors.

J Allergy Clin Immunol Pract 2021 05 29;9(5):1994-2000.e5. Epub 2020 Dec 29.

Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France; Equipe-EPAR-IPLESP, UMR 1136 INSERM, Sorbonne Université, Paris, France.

Background: Cephalosporins, which belong to the beta-lactam therapeutic class, are increasingly used throughout the world. Few large studies on this issue have been conducted, and most of them have been performed as part of penicillin hypersensitivity studies.

Objective: We described our 26-year experience exploring cephalosporin drug hypersensitivity, from which we identified epidemiological and cross-reactivity data.

Methods: We included 476 patients who reported drug hypersensitivity reaction (DHR) to cephalosporin and underwent an allergy workup between January 1992 and July 2018 in the Allergy Unit of the University Hospital of Montpellier (France). According to their structural side chain R1 homology, we worked with 4 classes of cephalosporins. Logistic regression analysis was used to search for risk factors for hypersensitivity to cephalosporin (positive skin test [ST] or drug provocation test [DPT] results).

Results: Cephalosporin hypersensitivity was proven in 22.3% of the patients referred in our Unit, according to positive ST (51.9%) or DPT to the culprit drug (48.1%). One in 5 patients were children, and cephalosporin hypersensitivity was confirmed in 15% (47.6% of them by means of ST). In the cephalosporin hypersensitive population, initial reactions were mostly immediate (68.9%) and anaphylactic (72.7%). Cross-reactivity with aminopenicillins was the most frequent pattern of cross-reactivity. In multivariate analysis, immediate reactions (odds ratio [OR] = 3, 95% confidence interval [CI] [1.6-5.5], P < .001), anaphylactic shock (OR = 6.5, 95% CI [3.3-13.1], P < .001) and anaphylaxis (OR = 3.1, 95% CI [1.6-6.1], P < .001), and multiple reactions to the same or several cephalosporins (OR = 2.0, 95% CI [1-3.5], P = .04) were statistically associated with confirmed DHR. DPT was generally safe, but elicited anaphylaxis in 20% of patients. Systemic reactions during skin testing occurred in 9.1% of positive patients, almost always related to anaphylactic index reactions. Nonimmediate confirmed DHR to cephalosporins were rare and occurred in less than 10% of the positive patients.

Conclusion: Almost a quarter of the tested patients were confirmed as hypersensitive to cephalosporins; sensitivity of skin testing was 51.9%, and thus, half of the positive patients needed a DPT to prove the diagnosis.
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http://dx.doi.org/10.1016/j.jaip.2020.11.063DOI Listing
May 2021

Utility of drug provocation tests in the evaluation of quinolone hypersensitivity reactions.

J Allergy Clin Immunol Pract 2021 05 28;9(5):2097-2100.e2. Epub 2020 Dec 28.

Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, University of Montpellier, Montpellier, France; Institut Desbrest d'Epidémiologie et de Santé Publique-UA11 INSERM, University of Montpellier, Montpellier, France.

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http://dx.doi.org/10.1016/j.jaip.2020.10.067DOI Listing
May 2021

Delayed positive drug provocation tests to beta-lactams with flare-up reactions of skin tests sites.

Clin Exp Allergy 2021 03 22;51(3):499-502. Epub 2020 Dec 22.

Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France.

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http://dx.doi.org/10.1111/cea.13810DOI Listing
March 2021

Hypersensitivity to gadolinium-based contrast agents: A single-center retrospective analysis over 7 years.

J Allergy Clin Immunol Pract 2021 04 25;9(4):1746-1749.e2. Epub 2020 Nov 25.

Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, University of Montpellier, Montpellier, France; Institut Desbrest d'Epidémiologie et de Santé Publique, UMR INSERM - Université de Montpellier, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.11.023DOI Listing
April 2021

Anaphylaxis in children.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:8-10

University Hospital of Montpellier, Montpellier, France.

Anaphylaxis in children is a potential acute life-threatening systemic hypersensitivity reaction. Anaphylaxis fatality rate is estimated to be 0.65% to 2%. Food is the main anaphylaxis trigger in children, notably cow's milk, peanuts, and tree nuts. Mucocutaneous manifestations are observed in more than 90% of cases, but it is not essential for diagnosis. Deaths are rather secondary to the laryngeal edema, observed in 40%-50% of cases. Personal history of asthma, allergy to particular foods such as peanuts and tree nuts, and adolescence are known risk factors for anaphylaxis and more severe reactions. Epinephrine (adrenaline) is the medication of choice for the first-aid treatment of anaphylaxis. However, adrenaline auto-injectors (AAIs) are commercially available in only 32% of world countries. There are still considerable unmet needs in the field of anaphylaxis in children. Therefore, the Montpellier WHO Collaborating Centre aims to start the global action plan applied to anaphylaxis.
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http://dx.doi.org/10.1111/pai.13336DOI Listing
November 2020

Digital Allergy Card: Design and Users' Perceptions.

Stud Health Technol Inform 2020 Nov;275:226-227

University Hospital of Montpellier, France.

This paper presents the design and the users' perceptions of a Digital Allergy Card for recording, sharing and tracing information on drug allergies.
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http://dx.doi.org/10.3233/SHTI200729DOI Listing
November 2020

Delayed hypersensitivity to antiepileptic drugs in children.

Pediatr Allergy Immunol 2021 04 18;32(3):425-436. Epub 2020 Dec 18.

Faculty of Medicine, University Children's Hospital, University of Belgrade, Belgrade, Serbia.

Background: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy, but they can be associated with the development of mainly delayed/non-immediate hypersensitivity reactions (HRs). Although these reactions are usually cutaneous, self-limited, and spontaneously resolve within days after drug discontinuation, sometime HR reactions to AEDs can be severe and life-threatening.

Aim: This paper seeks to show examples on practical management of AED HRs in children starting from a review of what it is already known in literature.

Results: Risk factors include age, history of previous AEDs reactions, viral infections, concomitant medications, and genetic factors. The diagnostic workup consists of in vivo (intradermal testing and patch testing) and in vitro tests [serological investigation to exclude the role of viral infection, lymphocyte transformation test (LTT), cytokine detection in ELISpot assays, and granulysin (Grl) in flow cytometry. Treatment is based on a prompt drug discontinuation and mainly on the use of glucocorticoids.

Conclusion: Dealing with AED HRs is challenging. The primary goal in the diagnosis and management of HRs to AEDs should be trying to accurately identify the causal trigger and simultaneously identify a safe and effective alternative anticonvulsant. There is therefore an ongoing need to improve our knowledge of HS reactions due to AED medications and in particular to improve our diagnostic capabilities.
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http://dx.doi.org/10.1111/pai.13409DOI Listing
April 2021

Diagnostic procedures & practices in drug allergy/hypersensitivity: a survey of 13 Asian countries.

Asia Pac Allergy 2020 Oct 15;10(4):e36. Epub 2020 Oct 15.

Department of Pediatrics, Nippon Medical School, Tokyo, Japan.

Background: The issues and challenges in the diagnosis of drug allergy/hypersensitivity among children and adults in Asia are likely to be different from non-Asian countries.

Objective: To study the diagnostic modalities used in the evaluation and management of drug allergy/drug hypersensitivity reactions (DHRs) among member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI).

Methods: A questionnaire comprising 41 questions was circulated electronically to member societies and individual members of APAAACI between January 23, 2020 and March 6, 2020.

Results: Twenty-six respondents from 15 member societies and 1 individual member responded. European DHR guidelines were most commonly used. Skin prick and intradermal testing was used by 100%, with only 60% having access to commercial penicillin skin test reagents. -specific IgE tests were used by 75%, and basophil activation test by 56.3% for immediate DHR. Patch tests were used by 75% in contrast to lymphocyte transformation tests by 25% for nonimmediate DHR. Drug provocation tests were used by 68.8%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (93.3%). Human leukocyte antigen (HLA) genotype testing was mandatory among 25% respondents before new carbamazepine prescriptions, and 8.3% for allopurinol prescriptions.

Conclusions: There was increased use of skin testing for iodinated contrast media hypersensitivity and patch testing for nonimmediate DHR. HLA genotype testing prior to new carbamazepine, allopurinol and abacavir prescriptions remain variable despite strong associations for severe cutaneous adverse reactions with Asian ethnicity. Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across APAAACI member societies.
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http://dx.doi.org/10.5415/apallergy.2020.10.e36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610088PMC
October 2020

Biological treatments in allergy: prescribing patterns and management of hypersensitivity reactions.

J Allergy Clin Immunol Pract 2021 03 5;9(3):1396-1399.e2. Epub 2020 Nov 5.

Division of Allergy, Département de Pneumologie et Addictologie, University Hospital of Montpellier, Montpellier, France; Sorbonne Université, INSERM UMR-S 1136, IPLESP, Equipe EPAR, Paris, France; WHO Collaborating Centre on Scientific Classification Support, Montpellier, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.10.044DOI Listing
March 2021

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Ann Am Thorac Soc 2021 02;18(2):238-246

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV and the FEV/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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http://dx.doi.org/10.1513/AnnalsATS.202002-113OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020720PMC
February 2021

A Proposal from the Montpellier World Health Organization Collaborating Centre for Better Management and Prevention of Anaphylaxis.

J Allergy Clin Immunol Pract 2021 02 13;9(2):676-683.e1. Epub 2020 Oct 13.

Division of Allergy, Department of Pulmonology, University Hospital of Montpellier, Montpellier, France; Sorbonne Université, INSERM UMR-S 1136, IPLESP, Equipe EPAR, Paris, France; WHO Collaborating Centre on Scientific Classification Support, Montpellier, France.

Since the first description of anaphylaxis in 1902, its clinical importance as an emergency condition has been recognized worldwide. Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction characterized by rapid onset and the potential to endanger life through respiratory or circulatory compromise. It is usually, although not always, associated with skin and mucosal changes. Although the academic/scientific communities have advocated to promote greater awareness and protocols for the management of anaphylaxis based on best evidence, there are few efforts documenting feedback as to the success of these efforts. In this article, we review the key unmet needs related to the diagnosis and management of anaphylaxis, and propose a public health initiative for prevention measures and a timetable action plan that intends to strengthen the collaboration among health professionals and especially primary care physicians dealing with anaphylaxis, which can encourage enhanced quality of care of patients with anaphylaxis. More than calling for a harmonized action for the best management of anaphylaxis to prevent undue morbidity and mortality, the Montpellier World Health Organization Collaborating Centre here proposes an action plan as a baseline for a global initiative against anaphylaxis. We strongly believe that these collaborative efforts are a strong public health and societal priority that is consistent with the overarching goals of providing optimal care of allergic patients and best practices of allergology.
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http://dx.doi.org/10.1016/j.jaip.2020.09.062DOI Listing
February 2021

Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort.

J Allergy Clin Immunol 2021 05 13;147(5):1830-1837.e15. Epub 2020 Oct 13.

Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom; Liverpool University Hospitals Foundation National Health Service Trust, Liverpool, United Kingdom. Electronic address:

Background: β-lactam antibiotics are associated with a variety of immune-mediated or hypersensitivity reactions, including immediate (type I) reactions mediated by antigen-specific IgE.

Objective: We sought to identify genetic predisposing factors for immediate reactions to β-lactam antibiotics.

Methods: Patients with a clinical history of immediate hypersensitivity reactions to either penicillins or cephalosporins, which were immunologically confirmed, were recruited from allergy clinics. A genome-wide association study was conducted on 662 patients (the discovery cohort) with a diagnosis of immediate hypersensitivity and the main finding was replicated in a cohort of 98 Spanish cases, recruited using the same diagnostic criteria as the discovery cohort.

Results: Genome-wide association study identified rs71542416 within the Class II HLA region as the top hit (P = 2 × 10); this was in linkage disequilibrium with HLA-DRB1∗10:01 (odds ratio, 2.93; P = 5.4 × 10) and HLA-DQA1∗01:05 (odds ratio, 2.93, P = 5.4 × 10). Haplotype analysis identified that HLA-DRB1∗10:01 was a risk factor even without the HLA-DQA1∗01:05 allele. The association with HLA-DRB1∗10:01 was replicated in another cohort, with the meta-analysis of the discovery and replication cohorts showing that HLA-DRB1∗10:01 increased the risk of immediate hypersensitivity at a genome-wide level (odds ratio, 2.96; P = 4.1 × 10). No association with HLA-DRB1∗10:01 was identified in 268 patients with delayed hypersensitivity reactions to β-lactams.

Conclusions: HLA-DRB1∗10:01 predisposed to immediate hypersensitivity reactions to penicillins. Further work to identify other predisposing HLA and non-HLA loci is required.
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http://dx.doi.org/10.1016/j.jaci.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100096PMC
May 2021
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